A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Ahmad K Haidar,Nikolaj S Troelsen,Niels D Kjeldsen,Kasper P Lundquist,Thomas O Larsen,Mads H Clausen,Viola Previtali

doi:10.3390/molecules27020521

Ahmad K Haidar, Nikolaj S Troelsen + Show 5 more

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https://doi.org/10.3390/molecules27020521

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Abstract

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.

Highlights

IntroductionThe fuoroisoquinoline fuoroisoquinoline alkaloidThe alkaloid TMC-120B TMC-120B (1)(1) was was first first isolated isolated from from the the fungus fungus AsAspergillus ustus al.al. (Figure1) [1].1)TMC-120B was initially discovpergillus ustus by byKamutsubaraKamutsubaraetet in 1999[1]
Epilepsy scribes a group of serious neurological disorders thatthat are characterized by recurrent epidescribes a group of serious neurological disorders are characterized by recurrent epileptic seizures has been estimated to affect as many as 50 million leptic seizures and and has been estimated to affect as many as 50 million people people worldworldwide
Reactions were monitored by thin layer chromatography (TLC) and/or reversed-phase ultra-performance liquid chromatography mass spectrometry (RP-UPLC-MS)

Summary

Introduction

1) [1].1)TMC-120B was initially discovpergillus ustus by byKamutsubara. TMC-120B was initially ered as a modulator of interleukin-5 mediated eosinophil viability [2], but discovered as a modulator of interleukin-5 mediated eosinophil viability [2],has butrecently has rebeen reported to exhibit antiepileptic activity in a Zebrafish model [3]. Epilepsy decently been reported to exhibit antiepileptic activity in a Zebrafish model [3]. Epilepsy scribes a group of serious neurological disorders thatthat are characterized by recurrent epidescribes a group of serious neurological disorders are characterized by recurrent epileptic seizures has been estimated to affect as many as 50 million leptic seizures [4,5][4,5].

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